AFM24 + Atezolizumab for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+16 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Affimed GmbH
Must not be taking: Anticancer, Investigational, Mitomycin, others
Disqualifiers: Active malignancy, Radiation, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial is testing AFM24 with atezolizumab in patients with advanced cancers that have not responded to other treatments. The treatment works by helping the immune system recognize and attack cancer cells. Atezolizumab is used in various advanced cancers, including lung and breast cancer.
Will I have to stop taking my current medications?
The trial requires that you stop taking any systemic anticancer therapy, including investigational agents, at least 4 weeks before starting the study drug. If you are using certain drugs like mitomycin C or nitrosoureas, the period is 6 weeks, and for fluorouracil or small molecule targeted drugs, it's 2 weeks or 5 half-lives, whichever is longer.
What data supports the effectiveness of the drug Atezolizumab in combination with AFM24 for advanced cancer?
Atezolizumab has shown effectiveness in treating various cancers, such as bladder cancer and non-small cell lung cancer, by improving survival rates and response rates in patients. It works by blocking a protein that helps cancer cells hide from the immune system, allowing the body to better fight the cancer.12345
Is the combination of AFM24 and Atezolizumab safe for humans?
Atezolizumab, also known as Tecentriq, has been used in various cancer treatments and generally has an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation and liver issues. The safety of AFM24 in combination with Atezolizumab specifically may not be fully established, but Atezolizumab alone has been considered safe in multiple studies.13467
How is the AFM24 + Atezolizumab drug unique for advanced cancer?
The combination of AFM24 and Atezolizumab is unique because it combines a novel treatment (AFM24) with Atezolizumab, a drug that blocks PD-L1, a protein that helps cancer cells evade the immune system. This combination aims to enhance the immune system's ability to fight cancer, offering a potentially new approach for patients with advanced cancer.12358
Eligibility Criteria
This trial is for adults with advanced or metastatic EGFR-positive cancers, like NSCLC, gastric/GEJ adenocarcinoma, HCC, hepatobiliary-, or pancreatic cancer that's worsened after treatment. They must have had certain prior therapies and good organ function. People can't join if they've had recent radiation therapy, active malignancies (with some exceptions), recent anticancer treatments, are using traditional Chinese medicine for tumors, or are in another clinical study.Inclusion Criteria
I have advanced liver, bile duct, or pancreatic cancer and have tried at least one standard treatment.
My organs are working well.
Phase 1: Evaluable or measurable disease per RECIST v1.1
See 3 more
Exclusion Criteria
I have no active cancers except for certain treated or non-threatening types.
I haven't had radiation therapy in the last 2 weeks or still have side effects from it.
I haven't taken any cancer drugs or traditional Chinese medicine for cancer in the last 2 to 6 weeks.
See 1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Lead-in
Participants receive a single dose of AFM24 and are observed for adverse events for 1 week
1 week
Dose Escalation
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab using a 3+3 design
Estimated up to 36 weeks
Expansion
Collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab
Estimated up to 36 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- AFM24 (Monoclonal Antibodies)
- Atezolizumab (Checkpoint Inhibitor)
Trial OverviewThe AFM24-102 study tests the combination of a new drug called AFM24 with an existing cancer medication Atezolizumab in patients with specific advanced solid tumors expressing EGFR. It's an open-label Phase 1/2a trial where all participants receive the drugs to evaluate safety and effectiveness at different doses.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Expansion PhaseExperimental Treatment2 Interventions
The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.
Group II: Escalation PhaseExperimental Treatment2 Interventions
The Escalation phase will determine the MTD/RP2D of AFM24 in combination with atezolizumab. A traditional 3+3 design will be used to determine the RP2D.
AFM24 is already approved in United States for the following indications:
🇺🇸 Approved in United States as AFM24 for:
- Advanced and/or metastatic EGFR-expressing non-small cell lung cancer (NSCLC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns HopkinsBaltimore, MD
Johns Hopkins UniversityBaltimore, MD
USC Norris Comprehensive Cancer CenterLos Angeles, CA
University of Chicago Medical CenterChicago, IL
Loading ...
Who Is Running the Clinical Trial?
Affimed GmbHLead Sponsor
References
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.
Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]Atezolizumab (Tecentriq®), an immune checkpoint inhibitor against programmed death ligand 1 (PD-L1), is the first immunotherapy agent to be approved (for use in combination with nab-paclitaxel) in the USA, the EU (as first-line) and Japan for the treatment of advanced triple-negative breast cancer (TNBC). Approval was based on the results of the phase III IMpassion130 trial in patients with unresectable locally advanced or metastatic TNBC, in which atezolizumab plus nab-paclitaxel significantly prolonged progression-free survival (PFS) when compared to placebo plus nab-paclitaxel in the intent-to-treat (ITT) population and the PD-L1+ subgroup. Statistically significant overall survival (OS) benefits were not seen in two interim analyses and final OS data are awaited. The tolerability and safety profile of atezolizumab plus nab-paclitaxel was consistent with those of each individual drug. The most common treatment-related adverse events included neutropenia, peripheral neuropathy and reduced neutrophil count. Adverse events of special interest occurred with higher frequency in patients who received atezolizumab plus nab-paclitaxel than placebo plus nab-paclitaxel, and were mostly immune-related (e.g. immune-related rash, hypothyroidism and hepatitis). Health-related quality of life was not significantly impacted by the addition of atezolizumab to nab-paclitaxel therapy. Thus, atezolizumab plus nab-paclitaxel is a useful immunochemotherapy option for patients with unresectable locally advanced or metastatic TNBC, including those whose tumours have PD-L1 expression ≥ 1%.
Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. [2020]Atezolizumab (Tecentriq®), a humanized, anti-programmed cell death ligand-1 (PD-L1) monoclonal antibody, in combination with bevacizumab, carboplatin and paclitaxel (ABCP) or with carboplatin and nab-paclitaxel (ACnP) has been approved as first-line treatment for metastatic nonsquamous NSCLC, based on results from the randomized IMpower150 and IMpower130 studies in chemotherapy-naïve patients with nonsquamous metastatic NSCLC. In IMpower150, ABCP prolonged progression-free survival (PFS) and overall survival (OS) relative to BCP, regardless of EGFR or ALK status, liver metastases at baseline or PD-L1 expression levels. In IMpower130, ACnP prolonged PFS and OS relative to CnP in patients without EGFR or ALK genetic aberrations. ABCP and ACnP had manageable tolerability profiles, which were consistent with the profile of the individual components of the regimen. Immune-related adverse events with ABCP and ACnP were largely mild or moderate in severity, and most were reversible with interruption of atezolizumab and initiation of appropriate treatment. Current evidence indicates that ABCP and ACnP are valuable emerging first-line treatment options for metastatic nonsquamous NSCLC.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.
Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.
Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. [2023]Purpose: Atezolizumab is a programmed death ligand 1 (PDL-1) blocking antibody that was approved for metastatic non-small cell lung cancer (NSCLC) in patients with disease progression. Various studies have been initiated to explore the effectiveness of atezolizumab among different patient cohorts and disease statuses, including as first-line therapy. The purpose of this paper is to identify and summarize the trials that use atezolizumab as a first-line agent in chemotherapy-naïve patients with NSCLC. Methods: A database search was performed on Pubmed, Embase, and Wiley Cochrane Library-Central Register of Controlled Trials to identify clinical trials using atezolizumab as first-line therapy in NSCLC. Additionally, ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) were searched to identify relevant clinical trials. Conference abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the American Association for Cancer Research were hand-searched. Any trial in which atezolizumab was used as first-line therapy in chemotherapy-naive patients with NSCLC was included. Results: Fifteen studies were ultimately included, all of which are current and ongoing. Of the 15 studies, 5 have reported results. When given in the first-line setting, atezolizumab had higher rates of objective response, progression-free survival, and overall survival, compared to the second and third-line settings. Among the 15 studies, atezolizumab is used as monotherapy (n = 5), in combination with chemotherapy (n = 6), in combination with targeted therapy such as bevacizumab (n = 1), as neoadjuvant/adjuvant therapy (n = 3), in combination with stereotactic body radiation therapy (n = 1), and in combination with or following chemoradiation (n = 1). Conclusion: Available evidence shows promising safety and efficacy with the use of atezolizumab as first-line therapy in NSCLC. Atezolizumab is currently being studied in a variety of treatment settings. If clinical benefits are shown, atezolizumab may deem to be a useful first-line agent in NSCLC.